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Epilepsy’s impact on cardiovascular function and autonomic regulation, including heart-rate variability, is complex and may contribute to sudden unexpected death in epilepsy (SUDEP). Lateralization of autonomic control in the brain remains the subject of debate; nevertheless, ultra-short-term heart-rate variability (HRV) analysis is a useful tool for understanding the pathophysiology of autonomic dysfunction in epilepsy patients. A retrospective study reviewed medical records of patients with temporal lobe epilepsy who underwent presurgical evaluations. Data from 75 patients were analyzed and HRV indices were extracted from electrocardiogram recordings of preictal, ictal, and postictal intervals. Various HRV indices were calculated, including time domain, frequency domain, and nonlinear indices, to assess autonomic function during different seizure intervals. The study found significant differences in HRV indices based on hemispheric laterality, language dominancy, hippocampal atrophy, amygdala enlargement, sustained theta activity, and seizure frequency. HRV indices such as the root mean square of successive differences between heartbeats, pNN50, normalized low-frequency, normalized high-frequency, and the low-frequency/high-frequency ratio exhibited significant differences during the ictal period. Language dominancy, hippocampal atrophy, amygdala enlargement, and sustained theta activity were also found to affect HRV. Seizure frequency was correlated with HRV indices, suggesting a potential relationship with the risk of SUDEP.

Background and Purpose: Perampanel is approved for the adjunctive treatment of focal-onset seizures (FOS) with or without secondary generalized seizures. The FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074) study evaluated the efficacy and safety of perampanel added to monotherapy in patients with FOS with or without secondary generalized seizures (SGS). Post hoc analyses of the FAME study assessed potential predictors of response and an in-depth evaluation of the safety and efficacy of perampanel.Methods: Efficacy was assessed by reduction of total seizure frequency by ≥50%, ≥75% or 100%, and safety by incidence of treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation. Univariate and multivariate logistic regression analyses for treatment response were performed.Results: Most patients (82/85) received perampanel doses of 4-8 mg/day during maintenance therapy and the highest efficacy rates were achieved with 4 mg/day, irrespective of efficacy outcome. Doses of 4 or 6 mg/day in patients with FOS with SGS (n=16) produced comparable efficacy outcomes. In multivariate analysis, total perampanel dose was predictive of 50% and 75% response rates; longer total perampanel administration period with 50% response; and concomitant non-anti-seizure medication with a 100% response. Patients developed a TEAE more frequently during the 12-week titration period (60.2%) than the 24-week maintenance period (28.4%), including dizziness (45.5% vs. 9.1%), somnolence (10.2% vs. 0%), and headache (4.5% vs. 3.4%).Conclusions: Post hoc analyses show that even low doses of perampanel may be effective and TEAEs are usually self-limited or well-tolerated.

Background and Purpose: FAME (Fycompa® as first Add-on to Monotherapy in patients with Epilepsy; NCT02726074), a previously reported single-arm, phase IV study, showed that perampanel improved seizure control as first add-on to failed anti-seizure medication (ASM) monotherapy in 85 South Korean patients aged ≥12 years with focal-onset seizures (FOS) with/without focal to bilateral tonic-clonic seizures. We present results of three post hoc analyses of FAME that further assessed the efficacy and safety of perampanel.Methods: Patients were stratified by low- (4, 6 mg/day) versus high- (8, 10, 12 mg/day) dose maintenance perampanel, perampanel added to first- versus second-line ASM monotherapy, and concomitant background ASM monotherapy and perampanel dose. The primary endpoint was the proportion of patients with a ≥50% reduction in total seizure frequency during the 24-week maintenance period. Safety was assessed by the descriptive incidence of treatment-emergent adverse events (TEAEs).Results: In post hoc analyses, 50% responder rates were significantly higher for low- versus high-dose maintenance perampanel (88.6% vs. 40.0%; p

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

Cortico-cortical evoked potential (CCEP) mapping is a rapidly developing method for visualizing the brain network and estimating cortical excitability. The CCEP comprises the early N1 component the occurs at 10-30 ms poststimulation, indicating anatomic connectivity, and the late N2 component that appears at < 200 ms poststimulation, suggesting long-lasting effective connectivity. A later component at 200-1,000 ms poststimulation can also appear as a delayed response in some studied areas. Such delayed responses occur in areas with changed excitability, such as an epileptogenic zone. CCEP mapping has been used to examine the brain connections causally in functional systems such as the language, auditory, and visual systems as well as in anatomic regions including the frontoparietal neocortices and hippocampal limbic areas. Task-based CCEPs can be used to measure behavior. In addition to evaluations of the brain connectome, single-pulse electrical stimulation (SPES) can reflect cortical excitability, and so it could be used to predict a seizure onset zone. CCEP brain mapping and SPES investigations could be applied both extraoperatively and intraoperatively. These underused electrophysiologic tools in basic and clinical neuroscience might be powerful methods for providing insight into measures of brain connectivity and dynamics. Analyses of CCEPs might enable us to identify causal relationships between brain areas during cortical processing, and to develop a new paradigm of effective therapeutic neuromodulation in the future.

Without direct facial nerve (FN) stimulation, transcranial facial motor evoked potential (fMEP) may considerably reflect the functional integrity and postoperative outcome of FN in cerebellopontine surgery. This study investigated the “threshold method” of fMEP to prognosticate the FN function after large vestibular schwannoma (VS) surgery. The medical records from 58 patients with large VS (maximal diameter > 2.5 cm) who underwent microsurgical resection were retrospectively reviewed. The threshold was the stimulation intensity to elicit the baseline amplitude of fMEP, and its change from the baseline to the end of surgery was defined as the delta fMEP. House-Brackman grade (HBG) of FN was documented at 1 week, 1 month, 6 months, and 1 year after surgical resection, classifying the patients presenting HBG 3 or more as FN dysfunction group. Receiver operating characteristics and binary logistic regression for the risk of postoperative FN dysfunction were performed. During surgery, the fMEP stimulation threshold increased in 27 (46%) patients. The delta fMEP value for FN dysfunction had a higher predictive value at long-term follow-up (cut-off = 15V, area under curve [AUC] 0.82 and 0.81 at postoperative 6 months and 1 year, respectively) than at the short-term follow-up (cut-off = 27.5V, AUC 0.78 and 0.74 at postoperative 1 week and 1 month, respectively). In regression analysis, the delta fMEP higher than its optimal cut-off was significantly associated with FN dysfunction in all follow-up period. These results suggested that the delta fMEP may serve as a valuable indicator of FN dysfunction after surgical resection of large VS, especially for long-term outcomes.

OBJECTIVE The anterior thalamic nucleus (ATN) is a common target for deep brain stimulation (DBS) for the treatment of drug-refractory epilepsy. However, no atlas-based optimal DBS (active contacts) target within the ATN has been definitively identified. The object of this retrospective study was to analyze the relationship between the active contact location and seizure reduction to establish an atlas-based optimal target for ATN DBS. METHODS From among 25 patients who had undergone ATN DBS surgery for drug-resistant epilepsy between 2016 and 2018, those who had follow-up evaluations for more than 1 year were eligible for study inclusion. After an initial stimulation period of 6 months, patients were classified as responsive (≥ 50% median decrease in seizure frequency) or nonresponsive (< 50% median decrease in seizure frequency) to treatment. Stimulation parameters and/or active contact positions were adjusted in nonresponsive patients, and their responsiveness was monitored for at least 1 year. Postoperative CT scans were coregistered nonlinearly with preoperative MR images to determine the center coordinate and atlas-based anatomical localizations of all active contacts in the Montreal Neurological Institute (MNI) 152 space. RESULTS Nineteen patients with drug-resistant epilepsy were followed up for at least a year following bilateral DBS electrode implantation targeting the ATN. Active contacts located more adjacent to the center of gravity of the anterior half of the ATN volume, defined as the anterior center (AC), were associated with greater seizure reduction than those not in this location. Intriguingly, the initially nonresponsive patients could end up with much improved seizure reduction by adjusting the active contacts closer to the AC at the final postoperative follow-up. CONCLUSIONS Patients with stimulation targeting the AC may have a favorable seizure reduction. Moreover, the authors were able to obtain additional good outcomes after electrode repositioning in the initially nonresponsive patients. Purposeful and strategic trajectory planning to target this optimal region may predict favorable outcomes of ATN DBS.

This study aims to compare directed transfer function (DTF), which is an effective connectivity analysis, derived from scalp EEGs between responder and nonresponder groups implanted with vagus-nerve stimulation (VNS). Twelve patients with drug-resistant epilepsy (six responders and six nonresponders) and ten controls were recruited. A good response to VNS was defined as a reduction of ≥50% in seizure frequency compared with the presurgical baseline. DTF was calculated in five frequency bands (delta, theta, alpha, beta, and broadband) and seven grouped electrode regions (left and right frontal, temporal, parieto-occipital, and midline) in three different states (presurgical, stimulation-on, and stimulation-off states). Responders showed presurgical nodal strength close to the control group in both inflow and outflow, whereas nonresponders exhibited increased inward and outward connectivity measures. Nonresponders also had increased inward and outward connectivity measures in the various brain regions and various frequency bands assessed compared with the control group when the stimulation was on or off. Our study demonstrated that the presurgical DTF profiles of responders were different from those of nonresponders. Moreover, a presurgical normal DTF profile may predict good responsiveness to VNS.

This study aimed to analyze the effect of wearing a mouthguard or not on masticatory muscle tone and stiffness of male taekwondo athletes during high-intensity weight training. The participants were male taekwondo athletes and aged 18 to 22 years. We randomly divided 24 men into the control group (CON; without a mouthguard; n=12) and the experimental group (MOG; with a mouthguard; n=12). Masticatory muscle tone and stiffness were measured after weight training at a level of 70% of one-repetition maximum. As a result of this study, masticatory muscle tone was no different in intragroup and intergroup after experiment. In addition, although the masticatory muscle stiffness was significantly higher in the dominant side of the MOG, there was no difference in intergroup, intragroup, and interaction. Through this study, it is necessary to consider the selective wearing of a mouthguard according to the training methods when partially analyzed from the physiological point of view of the masticatory muscle of taekwondo athletes.

The significance of interictal epileptiform discharges (IEDs) observed in the extratemporal lobe has not been fully evaluated in patients with mesial temporal lobe epilepsy (MTLE). This study aimed to evaluate the surgical outcomes, clinical features, and functional neuroimaging characteristics of patients in relation to the presence or absence of extratemporal IED in MTLE with hippocampal sclerosis (HS).A total of 165 patients with HS-induced MTLE who had undergone anterior temporal lobectomy were enrolled and stratified into the extratemporal interictal epileptiform discharges (ETD) and the temporal lobe discharges (TD) groups. We analyzed the differentiating features of pre- and postsurgical evaluation data between the two groups. For outcome assessment, only patients with a follow-up of at least 2 years were enrolled, and the outcomes were classified based on Engel classification.The ETD group showed extensive glucose hypometabolism involving the temporal lobe and extratemporal regions (p 0.001), and IEDs were observed bilaterally or contralateral to the ictal focus (p = 0.02). However, there was no difference in the surgical outcomes between the two groups. On multivariate analysis, statistically significant variables related to ETD occurrence including seizure onset age were not identified nevertheless.Our results indicate that ETD had a surgical outcome comparable to that of TD. Therefore, a surgical intervention need not be delayed even if extratemporal IED may be found in presurgical long-term scalp EEG monitoring.

Sea trial tests are necessary to verify speed-power performance, and are an import contract between ship owners and shipyards. The International Organization for Standardization (ISO) published ISO 15016:2015, which specifies the correlation method between model and full-scale ships. The results of sea trials have been questioned because of the uncertainty of speed and power measurements, especially when sea conditions differ from ideal calm water conditions. In this paper, such uncertainties were investigated by utilizing the standard speed-power trial analysis procedure defined in ISO 15016:2015 through Monte Carlo simulations. It was found that the expanded uncertainty of the delivered power (PDid) at 95 % confidence interval (k = 2) was ±1.5 % under 75 % MCR conditions.

Levetiracetam is a new antiepileptic drug (AED) used for treating and preventing partial or generalized seizures. The usefulness of levetiracetam therapeutic drug monitoring (TDM) is related to inter- or intra-individual pharmacokinetic variability, drug interactions, and patient noncompliance. We aimed to investigate the levetiracetam TDM status in Korean epilepsy patients. Serum trough levetiracetam concentrations were measured using liquid chromatography–tandem mass spectrometry in 710 samples from 550 patients. The median (range) daily and weight-adjusted levetiracetam doses were 1500 (20–5000) mg and 25.5 (3.03–133.0) mg/kg, respectively. Patients on levetiracetam monotherapy constituted only 19.5% of the population, while 30.1% were on co-medication with valproate and 56.0% with enzyme-inducing AEDs (EIAEDs). Observed levetiracetam concentrations were widely distributed, ranging 0.8–95 mg/L, with a median of 17.3 mg/L. Levetiracetam concentrations were therapeutic, supra-therapeutic, and sub-therapeutic in 58.5% (n = 393), 11.6% (n = 78), and 29.9% (n = 201) of samples, respectively. There was a strong correlation between weight-adjusted levetiracetam dosage and concentrations (ρ = 0.6896, p < 0.0001). In this large-scale clinical study, a large inter-individual difference in levetiracetam pharmacokinetics was observed, and levetiracetam concentrations were influenced by EIAEDs. For individual dose adjustments and monitoring compliance, routine levetiracetam TDM is needed in epilepsy patients.

Deep brain stimulation (DBS) has provided new treatment options for refractory epilepsy; however, treatment outcomes of DBS in refractory epilepsy patients previously treated with vagus nerve stimulation (VNS) have not been clarified. Herein, treatment outcomes of DBS of the anterior nucleus of the thalamus (ANT-DBS) in patients who had previously experienced VNS failure are reported. Seven patients who had previously experienced VNS failure underwent ANT-DBS device implantation. VNS was turned off before DBS device implantation. Monthly seizure counts starting from baseline to 12–18 months after DBS were analyzed. Five (71.3%) of the 7 patients experienced a >50% reduction of seizure counts after DBS; 1 responder reached a seizure-free status after DBS therapy. Of the 2 nonresponders, 1 subject showed improvement in seizure strength and duration, which lessened the impact of the seizures on the patient’s quality of life. This is the first study in which favorable outcomes of ANT-DBS surgery were observed in individual patients with refractory epilepsy who had not responded to prior VNS. Further studies with a larger number of subjects and longer follow-up period are needed to confirm the feasibility of ANT-DBS in patients who have previously experienced VNS failure.

Background and Objectives: Abnormal epileptic discharges in the brain can affect the central brain regions that regulate autonomic activity and produce cardiac symptoms, either at onset or during propagation of a seizure. These autonomic alterations are related to cardiorespiratory disturbances, such as sudden unexpected death in epilepsy. This study aims to investigate the differences in cardiac autonomic function between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE) using ultra-short-term heart rate variability (HRV) analysis around seizures. Materials and Methods: We analyzed electrocardiogram (ECG) data recorded during 309 seizures in 58 patients with epilepsy. Twelve patients with FLE and 46 patients with TLE were included in this study. We extracted the HRV parameters from the ECG signal before, during and after the ictal interval with ultra-short-term HRV analysis. We statistically compared the HRV parameters using an independent t-test in each interval to compare the differences between groups, and repeated measures analysis of variance was used to test the group differences in longitudinal changes in the HRV parameters. We performed the Tukey–Kramer multiple comparisons procedure as the post hoc test. Results: Among the HRV parameters, the mean interval between heartbeats (RRi), normalized low-frequency band power (LF) and LF/HF ratio were statistically different between the interval and epilepsy types in the t-test. Repeated measures ANOVA showed that the mean RRi and RMSSD were significantly different by epilepsy type, and the normalized LF and LF/HF ratio significantly interacted with the epilepsy type and interval. Conclusions: During the pre-ictal interval, TLE patients showed an elevation in sympathetic activity, while the FLE patients showed an apparent increase and decrease in sympathetic activity when entering and ending the ictal period, respectively. The TLE patients showed a maintained elevation of sympathetic and vagal activity in the pos-ictal interval. These differences in autonomic cardiac characteristics between FLE and TLE might be relevant to the ictal symptoms which eventually result in SUDEP.

Background and Purpose: Individualized anti-epileptic drug (AED) selection in patient with epilepsy is crucial. However, there is no unified opinion in treating patients with drug resistant epilepsy (DRE). This survey aimed to make a consolidate consensus with epileptologists’ perspectives of the treatment for Korean DRE patients by survey responses.Methods: The survey was conducted with Korean epilepsy experts who have experience prescribing AEDs via e-mail. Survey questionnaires consisted of six items regarding prescription patterns and practical questions in treating patients with DRE in Korea. The research period was from February 2021 to March 2021.Results: The survey response rate was 83.3% (90/108). Most (77.8%) of the responders are neurologists. The proportion of patients whose seizures were not controlled by the second AED was 26.9%. The proportion of patients who had taken five or more AEDs is 13.9%, and those who are currently taking five or more AEDs are 7.3%, of which 54.5% and 37.9% reported positive effects on additional AED, respectively. The majority (91.1%) of respondents answered that the mechanism of action was the top priority factor when adding AED. Regarding data priority, responders considered that expert opinion should have the top priority, followed by clinical experiences, reimbursement guidelines and clinical evidence. Responders gave 64.9 points (range from 0 to 100) about overall satisfaction on reimbursement system of Health Insurance Review and Assessment Service for AED.Conclusions: This study on AED therapy for DRE patients is the first nationwide trial in Korean epilepsy experts. In five drug failure, the top priorities on AED selection are mechanism of action and expert opinion. These findings might help to achieve consensus and recognize the insight on optimal therapy of AED in DRE.

Present paper deal with data analysis of on-board measurement data from operating ship. The main purpose of the study is estimating speed-power performance of target ship which are in service now. Various kinds of on-board measured data are considered such as ship speed, engine RPM, brake power, draught, rudder angle, etc. Also, in order to estimate the added resistance, weather forecast data about wind, wave and current was considered. What this study found was that the onboard measurement data and weather forecast data have a lot of uncertainty, so the data need to be post-processed in order to derive reliable speed power performance curve. For this reason, current study proposed three-step filtering procedure. The filtering schemes are based on 1) absolute threshold value, 2) moving window, 3) derivative threshold value. The paper compared the performance estimation results of ship with and without filtering technique and some conclusions could be drawn.

A novel minimally invasive wirelessly powered medical device, a magnetic induction extra-cranial brain stimulation (MI-ECBS) system is implemented for treating neurological disorders, Alzheimer’s disease (AD) and Epilepsy. The proposed system provides 2 different types of clinically significant stimulation waveforms for the therapy. For high frequency stimulation (HFS), we used 1mA, 10Hz, rectangular, charge balanced (0.5msec pulse width) pulses for 3sec with 21sec rest (total 600 pulses). Subsequently, under same configuration, a low frequency stimulation (LFS; 1Hz, 600 pulses) protocol was applied to canine-animal models. As a result, complementary neuro-modulation, facilitation and an inhibition are successfully demonstrated with an EEG power spectrum monitoring and the stimulation delivery efficacy is enhanced to 39.57x comparing to conventional transcutaneous direct current stimulation (tDCS).

Background and Objective: Epilepsy is one of the most common neurologic diseases worldwide, and 30% of the patients live with uncontrolled seizures. For the safety of patients with epilepsy, an automatic seizure detection algorithm for continuous seizure monitoring in daily life is important to reduce risks related to seizures, including sudden unexpected death. Previous researchers applied machine learning to detect seizures with EEG, but the epileptic EEG waveform contains subtle changes that are difficult to identify. Furthermore, the imbalance problem due to the small proportion of ictal events caused poor prediction performance in supervised learning approaches. This study aimed to present a personalized deep learning-based anomaly detection algorithm for seizure monitoring with behind-the-ear electroencephalogram (EEG) signals. Methods: We collected behind-the-ear EEG signals from 16 patients with epilepsy in the hospital and used them to develop and evaluate seizure detection algorithms. We modified the variational autoencoder network to learn the latent representation of normal EEG signals and performed seizure detection by measuring the anomalies in EEG signals using the trained network. To personalize the algorithm, we also proposed a method to calibrate the anomaly score for each patient by comparing the representations in the latent space. Results: Our proposed algorithm showed a sensitivity of 90.4% with a false alarm rate of 0.83 per hour without personal calibration. On the other hand, the one-class support vector machine only showed a sensitivity of 84.6% with a false alarm rate of 2.17 per hour. Furthermore, our proposed model with personal calibration achieved 94.2% sensitivity with a false alarm rate of 0.29 while detecting 49 of 52 ictal events. Conclusion: We proposed a novel seizure detection algorithm with behind-the-ear EEG signals via semi-supervised learning of an anomaly detecting variational autoencoder and personalization method of anomaly scoring by comparing latent representations. Our approach achieved improved seizure detection with high sensitivity and a lower false alarm rate.

Objective To examine a new abnormal muscle response (AMR) monitoring method during microvascular decompression (MVD) for hemifacial spasm. Methods 486 patients with hemifacial spasm were monitored for an AMR during MVD with a new method involving preoperative mapping and intraoperative centrifugal stimulation of the facial nerve. For the last 62 patients, we performed the AMR monitoring using both, the new and conventional methods simultaneously. Results Preoperative facial nerve mapping showed that the maximal AMR was detected most frequently (66.9%) at the “F” location (the direction towards the frontalis muscle). An intraoperative AMR was observed in 86.2% of the patients, which disappeared after MVD in 96.4% of the patients. A comparison of the new and conventional methods respectively showed that AMR disappearance after MVD was observed in 98.2% and 61.8% of the patients, no AMR in 0% and 9.1%, and persistent AMR after MVD in 1.8% and 29.1%. Conclusions The new AMR monitoring method demonstrated greater AMR monitoring efficacy and supports the finding that disappearance of an AMR is a good indicator of effective decompression during MVD surgery. Significance Preoperative mapping and intraoperative centrifugal stimulation of the facial nerve during MVD surgery in HFS patients showed greater efficacy of AMR monitoring.